In this grant proposal we focus on the function of a protein, CD2AP, which we have shown plays an important role in kidney glomerular function. This protein was originally cloned as a protein involved in T cell adhesion to antigen presenting cells. Surprisingly, CD2AP knockout mice die of nephrotic syndrome 6-7 weeks after birth. Its predominant expression in glomerular epithelial cells of the kidney and its ability to bind nephrin implicate CD2AP in the normal function of the slit diaphragm. In specific aim number 1, we propose to determine the specific pattern of CD2AP expression in the kidney in greater detail. In specific aim number 2, we propose to continue our analysis of homozygous and heterozygous CD2AP KO mice. We are particularly excited by our preliminary evidence suggesting that heterozygous CD2AP KO mice exhibit renal dysfunction. Lastly, in specific aim number 3, we propose to determine the function of CD2AP. Here we focus on defining the interaction of CD2AP with nephrin in greater detail and identifying protein partners for CD2AP. As glomerular epithelial specific genes are likely to play important roles in glomerular dysfunction, information from these studies are likely to lead to a better understanding of human renal disease.